The present invention relates to a pharmaceutical composition containing micronized progesterone, soya bean lecithin, and at least one oil selected from the group consisting of sunflower oil, olive oil, sesame seed oil, colza oil and almond oil. It also relates to pharmaceutical products comprising said pharmaceutical composition.
The invention also relates to the method for manufacturing this pharmaceutical composition, as well as to the uses thereof.
Progesterone is a hormone which is synthesized, in women, essentially by the ovary during the postovulation or luteal phase (more precisely by the cells of the corpus luteum) and, to a lesser degree, by the adrenal glands and the placenta during the second part of pregnancy. Non-endocrine synthesis of progesterone, in particular in neurons, is also possible.
A consequence of insufficiency of progesterone secretion in a woman is a loss of its biological effects: progestative effect, anti-androgen effect (action on the skin) and anti-oestrogen effect (the consequence being hyperoestrogenemia: hot flushes, psychogenic difficulties of the anxious or depressive type, weight gain, etc.). This progesterone insufficiency may lead to functional difficulties and diverse clinical manifestations, in particular:                premenstrual syndromes,        menstrual irregularities due to disovulation or anovulation,        benign mastopathies,        perimenopause and menopause.        
However, oral administration of progesterone suffers from a serious handicap due to the poor intestinal absorption and to the intense hepatic metabolism (short plasmatic half-life) of this hormone. Only the vaginal, rectal and intramuscular pathways would, to date, make it possible to maintain blood progesterone level at the physiological level of the luteal phase, for several hours.
The LABORATOIRES BESINS-ISCOVESCO have already proposed a solution in order to improve the quality and intensity of the digestive absorption of natural progesterone, in Patent Application FR 76 36007. Specifically, they have developed a formulation of soft capsules containing micronized progesterone in oily suspension. The synergistic effect of the micronization and the use of molecules containing long-chain fatty acids has made it possible to indisputably increase the bioavailability of progesterone taken orally. This formulation has known a great deal of success worldwide. It is sold in France under the trade mark UTROGESTAN®.
The oil which serves as a basis for the oily suspension in UTROGESTAN® is peanut oil.
Peanut (Arachis hypogae) is a leguminous plant, a bushy annual plant with yellow flowers, of the Papilionacea family.
In the last 15 years, peanut allergy has become a considerable allergological problem.
Dutau et al. (La Presse Médicale [Medical Press], vol. 28, p. 1553) observe that the prevalence of peanut allergy has recently been estimated at 1.3% in the general population. The increased use of peanut in food, very often in a masked form, perhaps explains this development.
Early sensitizations have been described in infants who have never consumed peanuts in conventional form, but who were apparently sensitized in utero or via maternal milk, through maternalized milks having contained plant fats (peanut oil) or through medicinal preparations in oily solution.
UTROGESTAN® may be prescribed in many cases of therapeutic indications, including as a supplement to the luteal phase during cycles of in vitro fertilization (IVF), and in the case of a danger of abortion or of prevention of repeat abortion due to luteal insufficiency, up to the 12th week of pregnancy. It is therefore possible, in theory, for a foetus to be exposed to UTROGESTAN® in utero.
To date, while the allergenic effects of peanut are definite, a controversy still exists regarding the ability of peanut oil to engender allergenic reactions. Many publications may be cited on this subject, including: Taylor et al., J. Allergy Clin. Immunol., vol. 68, p. 372 (1981); Moneret-Vautrin et al., Pediatr. Allergy Immunol. vol. 5, p. 184 (1994); Sabbah and Lauret, Allergic et Immunologic, vol. 26, p. 380 (1994); de Montis et al., Arch. Pédiatr., vol. 2. p. 25 (1995)).
Given this fact, the applicant company devoted itself to developing a novel pharmaceutical composition, replacing the peanut oil with other oils which do not have high risks of allergenicity, while at the same time endeavouring to conserve the advantages of the prior formula.